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Updated: Aug 16, 2026
Early Detection of Drug-Induced Renal Hemodynamic Dysfunction Using Sonographic Technology in Rats
Published on: March 11, 2016
Changes in renal function and oxidative damage in methamphetamine-treated rat
Itsuo Tokunaga1, Shin-ichi Kubo, Akiko Ishigami
1Department of Forensic Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.
Abstract:
In this study, we observed renal damage and peroxidative injury as the acute or sub-acute effect of methamphetamine (MA) to determine whether MA intoxication can be diagnosed from immunohistochemical changes in the kidney. In addition, renal function was investigated in relation to the immunohistochemical changes. A single administration of MA (group I) (50mg/kg/ (i.p.)) and repeated administration (group II) (10mg/kg/day (i.p.) for 5 days) were designed as an acute model and a sub-acute or chronic model. Immunohistochemically, cell damage markers were observed. Then, renal function markers and minerals in blood were measured. Myoglobin and creatinine phosphokinase (CPK) in blood were also analyzed. In group I, ubiquitin immunoreactivity was enhanced only in the renal tubules. Creatinine increased, while K, Ca, and P decreased (P<0.01). CPK increased significantly (P<0.01). Therefore, it was suspected that MA might induce renal dysfunction with renal tubule damage. This damage might be related to leakage of CPK from muscle. In group II, 8-hydroxy-2'-deoxyguanosine (8-OH-dG) increased immunohistochemically and quantitatively (P<0.01). It was considered that oxidative DNA damage might be induced by repeated administration. It was considered that this study offers basic information for the evaluation of pathological changes in the kidney in MA-related autopsy cases.
Insights
Methamphetamine (MA) causes kidney damage and peroxidative injury. Immunohistochemical changes in the kidney can help diagnose MA intoxication and assess renal function.
Area of Science:
- Nephrology
- Toxicology
- Forensic Pathology
Background:
- Methamphetamine (MA) use is associated with various health complications, including potential kidney damage.
- Understanding the specific renal effects of MA is crucial for diagnosis and treatment.
Purpose of the Study:
- To investigate the acute and sub-acute effects of MA on renal damage and function.
- To determine if immunohistochemical changes in the kidney can diagnose MA intoxication.
- To correlate renal function markers with observed immunohistochemical alterations.
Main Methods:
- Two MA administration models were used: single high dose (acute) and repeated lower doses (sub-acute/chronic).
- Immunohistochemistry was employed to detect cell damage markers in kidney tissue.
- Renal function markers, blood minerals, myoglobin, and creatinine phosphokinase (CPK) were measured.
Main Results:
- Acute MA exposure (single dose) enhanced ubiquitin immunoreactivity in renal tubules, increased creatinine, decreased electrolytes (K, Ca, P), and elevated CPK.
- Sub-acute/chronic MA exposure (repeated doses) led to increased 8-hydroxy-2'-deoxyguanosine (8-OH-dG), indicating oxidative DNA damage.
- Findings suggest MA induces renal dysfunction possibly linked to muscle damage (CPK leakage) and oxidative stress.
Conclusions:
- MA intoxication can cause renal tubule damage and dysfunction, evidenced by specific immunohistochemical markers.
- Oxidative DNA damage occurs with repeated MA administration.
- This research provides foundational data for evaluating kidney pathology in MA-related autopsy cases.
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